Synthesis of γ-difluoromethyl α,β-unsaturated γ-butyrolactones using PhSCF<inf>2</inf>SiMe<inf>3</inf>as a difluoromethylating agent

Abstract

Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. The synthesis of γ-difluoromethyl α,β-unsaturated γ-butyrolactones using PhSCF2SiMe3(1) as a difluoromethylating agent is described. The method involves the fluoride-catalyzed nucleophilic addition of 1 to a masked maleic anhydride 2 (cyclopentadiene-maleic anhydride adduct) to give key adduct 3. This adduct can be converted into γ-difluoromethyl α,β-unsaturated γ-butyrolactones 6 through reductive cleavage of the phenylsulfanyl group, stereoselecive nucleophilic addition reaction with Grignard reagents, followed by flash-vacuum pyrolysis. A general synthesis of γ-difluoromethyl α,β-unsaturated γ-butyrolactones is described. The method involves the fluoride-catalyzed nucleophilic addition of PhSCF2SiMe3to a masked maleic anhydride followed by reductive cleavage of the phenylsulfanyl group, reaction with Grignard reagents or NaBH4and flash-vacuum pyrolysis.